|Classification and external resources|
Haemoglobinopathy is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Hemoglobinopathies are inherited single-gene disorders; in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease. It is estimated that 7% of world's population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in ethnic populations from Africa, the Mediterranean basin and Southeast Asia.
Hemoglobinopathies imply structural abnormalities in the globin proteins themselves. Thalassemias, in contrast, usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some hemoglobinopathies are also thalassemias, but most are not.
Either hemoglobinopathy or thalassemia, or both, may cause anemia. Some well-known hemoglobin variants such as sickle-cell anemia and congenital dyserythropoietic anemia are responsible for diseases, and are considered hemoglobinopathies. However, many hemoglobin variants do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies, because they are not considered pathologies. Hemoglobin variants are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Other variants cause no detectable pathology, and are thus considered non-pathological variants.
Migration patterns (Alkaline Electrophoresis)
In general on alkaline electrophoresis in order of increasing mobility are hemoglobins A2, E=O=C, G=D=S=Lepore, F, A, K, J, Bart's, N, I, and H.
In general a sickling test (sodium bisulfite) is performed on abnormal hemoglobins migrating in the S location to see if the red cells precipitate in solution.
Migration patterns (Acid Electrophoresis)
In general on acid electrophoresis in order of increasing mobility are hemoglobins F, A=D=G=E=O=Lepore, S, and C.
This is how abnormal hemoglobin variants are isolated and identified using these two methods. For example a Hgb G-Philadelphia would migrate with S on alkaline electrophoresis and would migrate with A on acid electrophoresis, respectively
use of iso electric focusing to determine quantitative differences in globin chain synthesis and high performance liquid chromatograpgy that separates hemoglobins based on their various ffinities for the column
- Hb S
- Hb C
- Hb E
- Hb Bart's
- Hb D-Punjab
- Hb O-Arab
- Hb G-Philadelphia
- Hb Constant Spring
- Hb Hasharon
- Hb Korle-Bu
- Hb Lepore
- Hb M
- Hb Kansas
Hemoglobinopathy and evolution
Some hemoglobinopathies (and also related diseases like glucose-6-phosphate dehydrogenase deficiency) seem to have given an evolutionary benefit, especially to heterozygotes, in areas where malaria is endemic. Malaria parasites live inside red blood cells, but subtly disturb normal cellular function. In patients predisposed for rapid clearance of red blood cells, this may lead to early destruction of cells infected with the parasite and increased chance of survival for the carrier of the trait.
- Transport of oxygen from the lungs to the tissues: This is due to the peculiar cooperation of the globin chains that allows the molecule to take in more oxygen where there is increased oxygen and to release oxygen in low concentration of oxygen.
- Transport of carbon dioxide from the tissues to the lungs: The end product of tissue metabolism is acidic which increases hydrogen ions in solution. The hydrogen ions combine with bicarbonates to produce water and carbon dioxide. The carbon dioxide is mop up by hemoglobin to favor this reversible reaction.
- Transport of nitric oxide: Nitric oxide is a vasodilatator. This assists in the regulation of vascular reaction in times of stress as experienced during inflammation.
Pathology and organic structural abnormalities may lead to any of the following disease processes:
- Anemia due to reduced life span of the red cells of reduced production of the cells e. g. hemoglobin S, C and E.
- Increased oxygen affinity: The red blood cells do not release their oxygen content readily in hypoxic conditions. The bone marow therefore needs to produce more red blood cells and there is polycythemia.
- Unstable hemoglobins: Red blood cells are easily destroyed under stress and hemolysis occurs with possible jaundice.
- Methemoglobinemia: The iron in the heme portion of hemoglobin is easily oxidised and this reduces the ability of hemoglobin to bind oxygen. More deoxygenated hemoglobin are formed and the blood becomes cyanotic.
- "hemoglobinopathy" at Dorland's Medical Dictionary
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- "Hemoglobinopathies and Thalassemia". http://www.medicalassistantonlineprograms.org/. External link in
- "Hemoglobin Variants". Lab Tests Online. American Association for Clinical Chemistry. 2007-11-10. Retrieved 2008-10-12.
- Huisman THJ (1996). "A Syllabus of Human Hemoglobin Variants". Globin Gene Server. Pennsylvania State University. Retrieved 2008-10-12.
- Joseph Bonavetura and Austin Riggs, March 1968, "Hemoglobin Kansas, A Human Hemoglobin with a Neutral Amino Acid Substitution and an Abnormal Oxygen Equilibrium", The Journal of Biological Chemistry, Vol. 243, No. 5, Issue of March 10, pages 980-991.
- "rs33948057". dbSNP. National Center for Biotechnology Information. Retrieved 7 February 2014.